Candidatus Liberibacter asiaticus 3 4

14 The immune system is critical for keeping animals and plants healthy from 15 pathogens. However, immune-mediated diseases are also common for human. 16 Immune-mediated diseases have not been reported for plants. Here, we present 17 evidence that citrus Huanglongbing (HLB), caused by phloem-colonizing Candidatus 18 Liberibacter asiaticus (CLas), is an immune-mediated disease. CLas infection of 19 Citrus sinensis stimulated systemic and chronic immune response in the phloem 20 tissues including reactive oxygen species (ROS) production as indicated by H2O2, 21 callose deposition, and induction of immune related genes. Systemic cell death of 22 companion and sieve element cells, but not surrounding parenchyma cells, was 23 observed following ROS production triggered by CLas. ROS production triggered by 24 CLas localized in phloem tissues. The H2O2 concentration in exudates extracted from 25 phloem enriched bark tissue of CLas infected plants reached a threshold of killing 26 citrus protoplast cells, which was suppressed by uric acid (a ROS scavenger) and 27 gibberellin. Foliar spray of HLB positive citrus with antioxidants (uric acid and rutin) 28 and gibberellin significantly reduced both H2O2 concentrations and cell death in 29 phloem tissues induced by CLas and reduced HLB symptoms. RNA-seq analyses of 30 CLas infected and health C. sinensis support that CLas causes oxidative stress. In 31 sum, HLB is an immune-mediated disease and both mitigating ROS via antioxidants 32 and promoting plant growth can reduce cell death of the phloem tissues caused by 33 CLas, thus controlling HLB. 34